Tissue and cell development have been studied extensively to determine the mechanisms by which maturation, maintenance, and repair occur in living organisms. Generally, development of a cell or tissue can be considered as a transformation from one state or stage to another relatively permanent state or condition. Development encompasses a wide variety of developmental patterns, all of which are characterized by progressive and systematic transformation of the cells or tissue.
In many instances it is desirable to control or alter the development of cells and tissue in vivo to enhance the quality of life for higher organisms such as man. To this end, science has struggled to provide means by which the natural order of an organism can be maintained or restored in defiance of a debilitating injury, disease or other abnormality. While some prior art therapies have been successful, others have failed to reach their full potential due to unwanted side effects, inferior results, or difficult implementation.
As will be appreciated by those skilled in the art, tissue and organ development involve complex processes of cellular growth, differentiation and interaction mediated by complex biochemical reactions. At the genetic level, development is regulated by genomic expression; at the cellular level, the role of membrane interaction with the complex biochemical milieu of higher organisms is instrumental in development processes. Moreover, "remodeling" of tissues or organs is often an essential step in the natural development of higher organisms.
In recent years, multidisciplinary investigations of developmental processes have provided evidence suggesting that electric and magnetic fields play an important role in cell and tissue behavior. In U.S. patent application Ser. No. 923,760, now U.S. Pat. No. 4,818,697, entitled, "Techniques for Enhancing the Permeability of Ions," which has been assigned to the assignee of the present invention and the disclosure of which is incorporated herein by reference, a method and apparatus are disclosed by which transmembrane movement of a preselected ion is magnetically regulated using a time-varying magnetic field. The fluctuating magnetic field is tuned to the cyclotron resonance energy absorption frequency of the preselected ion. This important discovery brought to light the interplay of local geomagnetic fields and frequency dependence in ion transport mechanisms. It has now been discovered that by utilizing and extending the principles of cyclotron resonance tuning, an unexpected and remarkable advance in the control and modification of developmental processes in living tissue can be achieved.
Currently, research efforts in the area of electronic medical devices which affect growth mechanisms in living systems have focused on strain-related bioelectrical phenomena that have been observed in tissue such as bone, tendon and cartilage. During the last few decades, others have noted that electrical potentials are produced in bone in response to mechanical stress. It has been postulated that these electrical potentials mediate the stress-induced structural changes in bone architecture which were observed almost a century ago by J. Wolfe. Hence, although bioelectrical potentials are not well understood, numerous attempts have been made to induce tissue growth with electrical potentials and currents. Much of this work has dealt with the repair of bone non-unions, i.e. bone fractures which have not responded to traditional therapies.
Bone formation, as will be known by those skilled in the art, is a complex biological process. It involves the interaction of several characteristic cell types, including monocytes, osteoblasts, osteoclasts, osteocytes, chondrocytes, fibroblasts and undifferentiated bone mesenchymal cells which form a hard intercellular matrix of collagen and mineral crystals in which bone cells are embedded. The matrix is synthesized by osteoblasts which extrude collagen and mucopolysaccharide. By a process which is not fully understood, crystal nuclei form in the matrix to promote rapid mineralization by inorganic salts. Bone formation proceeds outward from ossification sites defined by clusters of osteoblasts. Osteoclasts then resorb bone during remodeling, whereby the bone architecture is restructured to provide maximum strength.
A number of bone disorders are known in which the integrity of the bone structure is compromised. Bone fractures produced by accidental trauma are quite common. The treatment of bone fractures may be complicated by delayed union of the fractured ends, by bone non-union, or by abnormal unions such as pseudarthroses. Moreover, in certain bone diseases, excess bone tissue is formed (osteophytes; osteosclerosis) which interferes with normal function. Alternatively, a shortage of bone tissue (osteopenia) may occur which decreases the fracture resistance of bone. A widespread, generalized form of osteopenia known as osteoporosis is characterized by a reduction in bone density accompanied by increased porosity and brittleness Osteoporosis is associated with a loss of calcium from bone and is a major concern of the elderly, a group in which the disease is most prevalent. Osteoporosis significantly increases susceptibility to bone fractures and is generally considered to be the most common bone disease in humans. Other maladies such as osteomalacia, Paget's disease, osteomyelitis and osteoarthritis are also well documented in medical literature.
A number of devices and techniques have been used by others with varying degrees of success to treat bone disorders. These include traction, splints, casts and internal fixation by pins and plates to repair bone fractures. Abnormal bone growth has been successfully interrupted by the fusion of the epiphysis to the bone shaft in a process referred to as "epiphysiodesis." Bone grafts have also been attempted with limited success. In some instances, where other treatment modalities fail, amputation of the affected limb is performed as a last resort.
More recently, methods have been explored by others for altering the electrical environment of bone tissue in an attempt to stimulate bone growth in fracture repair. These efforts originally concentrated on the use of electrode implants by which direct current was flowed across or into a bone non-union or abnormal union to stimulate repair. Due to numerous drawbacks, including the associated risks of surgery required to implant the electrodes, alternate, non-invasive techniques were pursued. While capacitively-generated electrostatic fields provided some beneficial resutls, the relatively large fields necessary were generally prohibitive. Finally, alternating, high-intensity electromagnetic fields were utilized to induce a voltage in bone. It was believed that by using the affected bone as a conductor, current flow through the bone could be induced which would produce therapeutic benefits.
These prior art inductive devices are typified by the apparatus disclosed in U.S. Pat. No. 3,893,462 to Manning entitled, "Bioelectrochemical Regenerator and Stimulator Devices and Methods for Applying Electrical Energy to Cells and/or Tissue in a Living Body" and the devices set forth in U.S. Pat. No. 4,105,017 to Ryaby et al. entitled, "Modification of the Growth Repair and Maintenance Behavior of Living Tissue and Cells by a Specific and Selective Change in Electrical Environment." These investigators have focused on the use of large fields to produce high induced currents in living tissue with well-defined "therapeutic" waveforms. The inventors of the present invention have approached the problem of regulating tissue growth from a different perspective. In its preferred embodiment, the present invention utilizes the interaction of fluctuating magnetic fields and preselected ions present in biological fluids to influence developmental processes. Although a possible role of magnetic fields beyond the galvanic action of induced currents is briefly mentioned in U.S. Pat. No. 3,890,953 to Kraus et al., to Applicants' knowledge no investigator has previously controlled bone growth in the manner set forth in the present invention.